Hollow microneedle arrays are being developed for transdermal drug delivery and the withdrawal of body fluids for biomedical and other applications. The hollow microneedle array can provide a minimally invasive means to transport relatively large molecules into and out of the skin. Microneedles are desirable because their small size and extremely sharp tip reduces insertion pain and tissue trauma to the patient. The length of the microneedles can be kept short enough to not penetrate to the pain receptors in the inner layers of the skin. Furthermore, the bore of the hollow microneedles can be large enough to provide a relatively rapid rate of drug delivery or withdrawal of bodily fluid. For drug delivery, the use of micron-size needle arrays increases skin permeability due to the needle's penetration of the outer layer of the skin, enabling the drugs to enter the body at therapeutically useful rates. Likewise, hollow microneedle arrays may replace painful hypodermic needles or syringes used for the sampling of biological fluids (e.g., blood or interstitial fluid). For example, for diabetics it is necessary to monitor and control blood sugar levels during the course of a day. The most common approach to monitor blood sugar is to stick the finger with a small needle and measure sugar level in the blood drop that forms at the site of the needle-stick. As a result, the patient may become sensitized to the frequent, painful needle-sticks, perhaps to the point of avoidance, and the sampling protocol is problematic. Microneedle arrays may enable the diabetic to routinely sample blood sugar levels in a pain-free manner.
With out-of-plane microneedles, the longitudinal axis of the microneedles is perpendicular to the wafer. These microneedles are typically short (e.g., less than a few hundred microns) and only penetrate the outer barrier layers of the skin. Out-of-plane needles can typically be made with a large density of needles per chip. Therefore, two-dimensional arrays of microneedles have been used to obtain adequate fluid flow at reasonable pumping rates. See, e.g., P. Zhang et al., “Micromachined Needles for Microbiological Sample and Drug Delivery System,” Proc. Intl. Conf. MEMS, NANO, and Smart Systems (ICMENS'03), Jul. 20–23, 2003, Banff, Alberta, Canada. However, only microneedles with the correct geometry and physical properties can be inserted into the skin. In particular, the safety margin for needle breakage, or the ratio of microneedle fracture force to skin insertion force, has been found to be optimum for needles having a small tip radius and large wall thickness. See M. R. Prausnitz, “Microneedles for transdermal drug delivery,” Advanced Drug Delivery Reviews 56, 581 (2004).
Microneedle arrays have been fabricated by a number of micromachining processes. Out-of-plane microneedles have typically been fabricated using bulk micromachining or LIGA techniques (LIGA is the German acronym for X-ray lithography, electrodeposition, and molding). Therefore, most of these microneedles have been made of silicon or metals. Silicon bulk micromachining has used either deep reactive ion etching (DRIE) alone or in combination with KOH etching to form the hollow microneedles. See H. J. G. E. Gardeniers et al., “Silicon Micromachined Hollow Microneedles for Transdermal Liquid Transport,” J. Microelectromechanical Systems 12(6), 855 (2003) and P. Griss et al., “Side-Opened Out-of-Plane Microneedles for Microfluidic Transdermal Liquid Transfer,” J. Microelectromechanical Systems 12(3), 296 (2003). However, these fabrication processes are long and difficult and can result in inconsistent wall slopes both in inside diameter and outside diameter of the hollow microneedles. Furthermore, the expensive capital equipment required is slow and not well-suited to eventual mass production of microneedles. Finally, at the end of the process, the silicon microneedles require oxidation so that only a biocompatible silicon dioxide surface is in contact with biological processes.
Therefore, a simple fabrication process using inexpensive equipment, providing repeatable results, and directly producing hollow microneedles in a biocompatible substrate is needed. The present invention provides a method to fabricate hollow microneedle arrays using a photoetchable glass wafer that solves these problems.